Porous composite biomaterials and related methods

ABSTRACT

Synthetic composite materials for use, for example, as orthopedic implants are described herein. In one example, a composite material for use as a scaffold includes a thermoplastic polymer forming a porous matrix that has continuous porosity and a plurality of pores. The porosity and the size of the pores are selectively formed during synthesis of the composite material. The example composite material also includes a plurality of a anisometric calcium phosphate particles integrally formed, embedded in, or exposed on a surface of the porous matrix. The calcium phosphate particles provide one or more of reinforcement, bioactivity, or bioresorption.

This application claims the benefit of U.S. Provisional PatentApplication Ser. No. 60/904,098, filed on Feb. 28, 2007, entitled“Reinforced Porous Polymer Scaffolds,” U.S. Provisional PatentApplication Ser. No. 60/939,256, filed on May 21, 2007, entitled“Interbody Spinal Fusion Cages Containing Anisometric Calcium PhosphateReinforcements and Related Methods,” and U.S. patent application Ser.No. 12/039,666, filed on Feb. 28, 2008, entitled “Porous CompositeBiomaterials and Related Methods,” each of which is incorporated hereinby reference in its entirety.

FIELD OF THE DISCLOSURE

The present disclosure relates generally to composite biomaterials andmore particularly to porous composite biomaterials and related methods.

BACKGROUND

Natural bone grafts such as autogenous bone grafts (autografts) arecommonly used in procedures for repairing or replacing bone defectsbecause they provide good structural support and osteoinductivity.Natural bone grafts involve removing or harvesting tissue from anotherpart of a host's body (e.g., typically from the iliac crest, hip, ribs,etc.) and implanting the harvested tissue in the defect site. Not onlydo these grafts require an added surgical procedure needed to harvestthe bone tissue, these grafts have limitations, including for example,transplant site morbidity. One alternative to autografts is allografts,which involve removing and transplanting tissue from another human(e.g., from bone banks that harvest bone tissue from cadavers) to thedefect site. However, allografts are known to induce infection andimmunotoxicity, suffer from limited supply and variability, and have alessened effectiveness because the cells and proteins that promote bonegrowth are lost during the harvesting process (e.g., during cleansingand disinfecting process). Demineralized bone matrix (DBM) is typicallyused to induce bone growth at defect sites, but DBM lacks the mechanicalproperties (e.g., stiffness, strength, toughness, etc.) necessary to beconsidered a viable option for load-bearing applications.

Synthetic bone substitute materials have been researched in thetreatment of diseased bone (e.g., osteoporosis), injured bone (e.g.,fractures), or other bone defects in lieu of natural bone grafts.Synthetic bone substitutes are viable alternatives to the moretraditional methods described above. However, synthetic substitutematerials used to repair diseased bones and joints should function orperform biologically and mechanically (i.e., as the structural supportrole of the bone itself) by, for example, mimicking the density andoverall physical structure of natural bone to provide a framework foringrowth of new tissue. One type or application of a synthetic bonesubstitute is a scaffold, which provides support for bone-producingcells. Scaffolds may be biodegradable, which degrade in vivo, or theymay be non-biodegradable to provide permanent implant fixation (e.g.,spinal fusion cages). In addition, scaffolds are typicallybiocompatible, and some may be bioactive, bioresorbable,osteoconductive, and/or osteoinductive. The shapability, deliverability,cost, and ability to match the mechanical properties of the surroundinghost tissue are other factors that vary among different types ofscaffolds and other bone substitutes.

Problems may arise when there is a mechanical mismatch between the bonesubstitute and the surrounding tissue. For example, metallic implantsand dense ceramics have mechanical properties that are typically anorder of magnitude greater than the bone tissue. As a result, a stiffmetal bone substitute implant acts to “shield” the adjacent bone tissuefrom mechanical stresses, resulting in a weakened bone at thebone-implant interface. Furthermore, efforts to utilize porous ceramicsor polymer bone cement in place of stiffer materials have been limited.For example, ceramics possess low fracture toughness, thereby making theorthopedic implant brittle (i.e., susceptible to fracture). Polymers arelimited by higher compliance and lower strength, thereby limiting theirability to support physiological load levels. Additionally, conventionalorthopedic implant biomaterials are not osteoconductive and bioactive,resulting in a lack of bonding between the implant and the peri-implanttissue.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A is a perspective view of an example porous composite materialdescribed herein.

FIG. 1B is a cross-sectional view of a portion of the example porouscomposite material of FIG. 1A.

FIG. 2A-2C are scanning electron micrographs of a portion of the exampleporous composite material shown in increasing magnification.

FIG. 3 is graphical representation of the elastic modulus of exampleapatite reinforced polymer composites versus the reinforcement volumefraction.

FIG. 4 shows scanning electron micrograph of a portion of the surface ofan example composite material reinforced with calcium phosphate whiskersembedded within and exposed on the surface, and schematically showingthe orientation of the whiskers relative to the loading direction of thematerial or scaffold strut.

FIG. 5A is a schematic illustration of a known spinal fusion cageinserted between spinal vertebrae.

FIG. 5B illustrates the example known spinal fusion cage of FIG. 5A.

FIG. 6 illustrates another example scaffold described herein.

FIG. 7 illustrates yet another example scaffold described herein.

FIG. 8 is a flow diagram illustrating an example process of creating anexample composite material apparatus described herein.

DETAILED DESCRIPTION

In general, the example methods, apparatus, and materials describedherein provide a biocompatible, bioactive synthetic porous composite foruse as synthetic bone substitute materials. The synthetic composite mayprovide a synthetic porous scaffold for use an orthopedic implant and/orbe injectable via percutaneous or surgical injection to cure in vivo.Because the example composite material is used to form a scaffold ormatrix that is used in an implantable device, the descriptions of one ormore of these structures may also describe one or more of the otherstructures. The synthetic porous composites are tailored to mimicbiological and mechanical properties of bone tissue for implantfixation, synthetic bone graft substitutes, tissue engineeringscaffolds, interbody spinal fusion, or other orthopedic applications. Anexample porous composite material described herein reduces subsidenceand/or bone resorption resulting from mechanical mismatch problemsbetween a synthetic scaffold of an implant device and the peri-implanttissue. Additionally, porosity and/or the pore sizes of the examplesynthetic composite are tailorable to specific applications toeffectively promote the vascularization and growth of bone in the poresand/or void spaces of the example scaffolds, thereby improving bondingbetween the scaffolds and peri-implant tissue.

The example composite material or scaffolds are synthesized or madethrough a process that enables reinforcement particles to be integrallyformed with or embedded within polymer matrices. In this manner, thepolymer matrices embedded with the reinforcement material provideimproved material properties (e.g., stiffness, fatigue strength, andtoughness). The reinforcement particles are also exposed on a surface ofthe matrices, which promotes bioactivity and/or bioresorption.Additionally, the process provides flexibility to tailor the level ofreinforcement particles and porosity for a desired application. Forexample, a porogen material may be used to vary the porosity, while thepore size is tailored by, for example, sieving the porogen to a desiredsize.

By varying the volume of the reinforcement particles and the porosity ofthe example scaffold, the mechanical properties (e.g., stiffness,strength, toughness, etc.) of the example scaffold of the implant devicemay be tailored to match those of the adjacent peri-implant bone tissueto reduce mechanical mismatch problems. Reducing mechanical mismatchprovides a decreased risk of subsidence, stress shielding, boneresorption, and/or subsequent failure of adjacent peri-implant bonetissue. Additionally, the example scaffold of the implant device mayinclude a significantly high porosity to promote bone ingrowth, whileexhibiting significantly higher effective mechanical properties such as,for example, the mechanical properties of trabecular bone.

In particular, the example composite material includes a continuousporous biocompatible matrix having a thermoplastic polymer matrixreinforced with anisometric calcium phosphate particles. Morespecifically, in one example, a composite material includes apolyetheretherketone (PEEK) or a polyetherketoneketone (PEKK) matrixreinforced with various volume fractions of hydroxyapatite (HA) whiskers(e.g., 20 or 40 volume percent), wherein the matrix is approximatelybetween 70% and 90% porous. In another example, the porous matrixincludes a biocompatible, microporous polymer cage reinforced withanisometric calcium phosphate particles and bone morphogenic protein(BMP) such as, for example, rhBMP-2, which can be dispersed oraccommodated by the void spaces and/or pores of the example porousscaffold and/or exposed on the surface of the example porous scaffold.Additionally, the BMP binds to the calcium phosphate further localizingthe BMP to the surface of the scaffold or matrix.

The example composite materials described herein may be used forapplications such as, for example, synthetic bone graft substitutes,bone ingrowth surfaces applied to existing implants, tissue engineeringscaffolds, interbody spinal fusion cages, etc. In each of theapplications, carrier materials (e.g., collagen, hydrogels, etc.)containing growth factors, such as BMP, may be incorporated into thepore space of the scaffold of the implant device to further enhanceosteoinduction and/or osteoconduction to promote osteointegration.

Human bone tissues exhibit substantial variation in mechanicalproperties depending on the tissue density and microstructure. Theproperties are highly dependent on anatomic location and apparentdensity of the measured specimen. For example, a femur includes acortical bone that has a relative porosity on the order of about 5-15%,and a trabecular bone that has a porosity on the order of about 75-95%.Due to the highly significant porosity differences, the trabecular boneexhibits significantly lower effective mechanical properties compared tothe cortical bone. Therefore, depending on the application, syntheticcomposite materials for use as scaffolds and/or spinal fusion cages orother implant devices should possess the mechanical properties exhibitedby the cortical bone or the trabecular bone, but must also haveeffective porosity to promote bone growth.

To avoid the mechanical mismatch problems, such as stress shielding, theexample scaffold of the implant device described herein may be tailoredto substantially match or mimic the mechanical properties (e.g.,stiffness, strength, toughness, etc.) of the adjacent and/or substitutedbone tissue. Several factors may be varied during the synthesis of thecomposite material and scaffold of the implant device to tailor themechanical properties including the calcium phosphate reinforcementvolume fraction, aspect ratio, size and orientation; the polymer; andthe size, volume fraction, shape and directionality of the void spaceand/or porosity. Tailoring the mechanical properties of the scaffoldreduces the likelihood of mechanical mismatch leading to a decreasedrisk of subsidence, stress shielding, bone resorption and/or subsequentfailure of adjacent vertebrae.

FIG. 1A illustrates the example synthetic porous composite material 100described herein. FIG. 1B is a cross-sectional view of a portion of theexample porous composite material 100 of FIG. 1A. The example syntheticcomposite material 100 provides a synthetic porous scaffold 101 for useor in as an orthopedic implant.

The example synthetic porous composite material 100 includes a porousthermoplastic polymer (e.g., a PEEK polymer) matrix 102 havinganisometric calcium phosphate reinforcement particles 104 integrallyformed or embedded with the matrix 102 and/or exposed on a surface ofthe matrix. In this manner, the polymer matrix 102 embedded with thereinforcement particles 104 provides high material strength, and thereinforcement particles 104 exposed on the surface of the matrix 102promote bioactivity and/or bioresorption. The porous polymer matrix 102includes a substantially continuous porosity and a plurality of pores106 to enable bone ingrowth into the porous matrix 102. In addition, thematrix 102 is substantially continuously interconnected via a pluralityof struts 108. Furthermore, at least one of the plurality of struts 108may be a load-bearing strut.

FIGS. 2A-2C are scanning electron micrographs showing increasingmagnification of a portion of an example scaffold 200 with struts 202.The example scaffold 200 is a PEEK scaffold reinforced with 40% byvolume HA whiskers 204. FIG. 2A illustrates the architecture or matrix206 of the scaffold 200 and FIG. 2B illustrates an enlarged portion ofthe struts 202. In the illustrated example, the HA whiskers 204 areintegrally formed and/or embedded within the matrix 206 of the scaffold200 for reinforcement. The HA whiskers 204 are also exposed on a surface208 of the matrix of the scaffold 200 for bioactivity and/orbioresorption, as noted above. As shown in FIG. 2C, the HA whiskers 204are aligned in a sheet texture and are exposed on the surface 208 of thestruts 202.

The thermoplastic polymer of the example scaffolds described herein maybe a biodegradable polymer for synthetic bone graft substituteapplications, or nonbiodegradable for implant fixation applications. Thethermoplastic polymer includes a continuous matrix of a compositematerial and is biocompatible and/or bioresorbable as described above.Additionally or alternatively, the polymer may be a radiolucent polymer,bioresorbable (i.e., a material capable of being resorbed by a patientunder normal physiological conditions) and/or non-bioresorbable, asdesired. Further, the thermoplastic polymer matrix may include a polymersuitable for injection via percutaneous or surgical injection so thatthe composite material 100 cures in vivo.

Suitable non-resorbable polymers include, without limitation,polyaryletherketone (PAEK), polyetheretherketone (PEEK),polyetherketonekteone (PEKK), polyetherketone (PEK), polyethylene, highdensity polyethylene (HDPE), ultra high molecular weight polyethylene(UHMWPE), low density polyethylene (LDPE), polyethylene oxide (PEO),polyurethane, polypropylene, polypropylene oxide (PPO), polysulfone,polypropylene, copolymers thereof, and blends thereof. Suitablebioresorbable polymers include, without limitation, poly(DL-lactide)(PDLA), poly(L-lactide) (PLLA), poly(glycolide) (PGA),poly(ε-caprolactone) (PCL), poly(dioxanone) (PDO), poly(glyconate),poly(hydroxybutyrate) (PHB), poly(hydroxyvalerate (PHV),poly(orthoesters), poly(carboxylates), polypropylene fumarate),poly(phosphates), poly(carbonates), poly(anhydrides),poly(iminocarbonates), poly(phosphazenes), copolymers thereof, andblends thereof. Suitable polymers that are injectible via percutaneousor surgical injection that cure in vivo include, without limitation,polymethylmethacrylate (PMMA), and other polyacrylics from monomers suchas bisphenol a hydroxypropylmethacrylate (bis-GMA) and/or tri(ethyleneglycol) dimethacrylate (TEG-DMA).

Although synthetic substitute composite materials made of polymerssatisfy the functional criteria of an implantable device because theyare, for example, formable and inexpensive, polymers alone lackbiological efficacy to promote bone growth and/or may lack requisitemechanical properties to support load levels. To increase the mechanicalproperties of the polymers, the polymers are reinforced with calciumphosphates. The aspect ratio, size, volume fraction and degree ofpreferred orientation of the calcium phosphate particles 104 (e.g., HAwhisker particles) may be tailored for the desired material propertiesand implant performance. For example, consider the information presentedin FIG. 3, which is a graphical illustration of the elastic modulus ofHA whisker and powder reinforced polymer composite materials versus thevolume fraction percentage of the apatite calcium phosphates that ismixed with the polymer matrix. The shaded areas of FIG. 3 showapproximate regions for the given mechanical property of the humancortical bone tissue. As depicted in the graph, the elastic modulus ofthe composite materials increases with increasing HA content. Inaddition, increasing the level of HA reinforcement in polymer compositesincreases cellular activity during osteointegration.

The calcium phosphate reinforcement particles 104 may be in the form ofsingle crystals or dense polycrystals, but are at least in some portionanisometric. “Anisometric” refers to any particle morphology (shape)that is not equiaxed (e.g., spherical), such as whiskers, plates,fibers, etc. Anisometric particles are usually characterized by anaspect ratio. For example, HA single crystals are characterized by theratio of dimensions in the c- and a-axes of the hexagonal crystalstructure. Thus, the anisometric particles in the present disclosurehave an aspect ratio greater than 1. In one example, the mean aspectratio of the reinforcement particles is from about 1 to about 100. Byfurther example, the reinforcement particles can be provided in anamount of from about 1% by volume of the composite biomaterial to about60% by volume, and for example, from about 20% by volume of thecomposite to about 50% by volume.

Due to their morphology, the calcium phosphate reinforcements particles104 may be oriented in bulk or near the surface of the polymer matrix102 to provide directional properties, if desired. For example, if thereinforcement particles 104 are predominately aligned within the matrix102 the morphological alignment of the particles 104 provides anisotropyfor the overall composite 100, which can be tailored to be similar tothe anisotropic mechanical properties of bone tissues. For example, FIG.4 shows a micrograph of anisometric calcium phosphate reinforcement 400on the surface of a dense composite polymer matrix 402. Also shown inFIG. 4 is a schematic illustration of a portion of matrix 402 andillustratively showing the orientation of the reinforcement particles400 relative to the loading direction of the material and/or a scaffoldstrut, which is, for example, at an angle θ.

Furthermore, there are no limits on the size or amount of the calciumphosphate particles 104 in matrix 102, provided that the calciumphosphate particles 104 are dispersed within and/or exposed at thesurface of the polymer matrix 102. For example, the reinforcementparticles 104 may have a maximum dimension from about 20 nm to about 2mm, and for example, between 20 nm to about 100 μm. While both nano- andmicro-scale calcium phosphate particles improve the mechanicalproperties of the example synthetic composite material 100 describedherein, nano-scale calcium phosphate particles are particularlyeffective for enhancing bioresorbability and cell attachment, andmicro-scale particles are particularly effective for obtaining a uniformdispersion within the matrix 102.

Suitable calcium phosphates may include, without limitation, calcium HA,HA whiskers, HA, carbonated calcium HA, beta-tricalcium phosphate(beta-TCP), alpha-tricalcium phosphate (alpha-TCP), amorphous calciumphosphate (ACP), octacalcium phosphate (OCP), tetracalcium phosphate,biphasic calcium phosphate (BCP), anhydrous dicalcium phosphate (DCPA),dicalcium phosphate dihydrate (DCPD), anhydrous monocalcium phosphate(MCPA), monocalcium phosphate monohydrate (MCPM), and combinationsthereof.

As described above, a synthetic composite material 100 not only bearsphysiological levels of load, but also promotes oseteointegration—thedirect structural and functional connection between the living bone andthe surface of the load-bearing implant. The bioactive calcium phosphateparticles 104 (e.g., HA whiskers) exposed on the surface of the exampleporous matrix 102 promote a stable bone-implant interface.Osteointegration also requires the vascularization and growth of boneinto an implant via interconnected and/or continuous porosity.

Thus, the size, volume fraction, shape, and directionality of the voidspaces and/or pores 106 may be tailored to optimize osteoconduction andimplant mechanical properties. The pores 106 may be any size or shape,while maintaining a continuous network to promote a fusion through theformation of new bone tissue in the void spaces and/or pores 106. Forexample, the pores 106 may be present throughout the matrix 102 asillustrated in FIG. 1A. Also, the pores 106 may be functionally gradedin any material or implant direction, for example, radially, as shown inFIGS. 6 and 7, from a highly porous region to a relatively dense region,or may include a void space. The change in porosity from one region toanother may be very distinct, for example as shown in FIGS. 6 and 7, orgradual. Furthermore, the graded change may be uniform or variant. Inaddition, instead of a graded change there may be a combination ofmaterials having two or more densities of pores. The central void may beany shape or size, and may receive (e.g., be filled) a material, astructure, or the composite material 100 (i.e., the composite materialgraded from the porous outer surface to a dense center), thereby forminga porous outer perimeter and a dense central region. Examples arefurther described in connection with FIGS. 6 and 7 below.

As discussed in greater detail below, the porosity and/or pore sizes 106may be selectively formed by the inclusion of, for example, a porogenmaterial during synthesis of the composite material 100. Pores spacesmay range from about 100 μm to about 500 μm, and, for example, fromabout 250 μm to about 500 μm. The example composite biomaterial 100 mayadditionally contain some fraction of microporosity within scaffoldstruts that is less than about 10 μm in size. The total amount ofporosity within porous regions may range from about 1% to about 90% byvolume, and, for example, between about 70% and 90% by volume. However,the porosity may also be tailored via other processes such as, forexample, microsphere sintering, fiber weaving, solvent casting,electrospinning, freeze drying (lyophilization), thermally induced phaseseparation, gas foaming, and rapid prototyping processes such as, forexample, solid freeform fabrication, robotic deposition (aka,robocasting), selective laser sintering, fused deposition modeling,three-dimensional printing, laminated object manufacturing,stereolithography, etc., or any other suitable process(es) orcombination(s) thereof.

Additionally, the example composite material 100 may optionally includeadditives, if desired. For example, the composite material 100 mayinclude one or more surface-active agents to enhance interfacial bondingbetween the reinforcement particles 104 and the polymer matrix 102. Thevoid spaces and/or pores 106 may accommodate and deliver one or moregrowth factors such as, for example, BMP, to enhance osteoinductivityand/or bone regeneration. Furthermore, the void spaces and/or pores 106may also accommodate and deliver one or more transcription factors,matrix metalloproteinases, peptides, proteins, bone cells, progenitorcells, blood plasma, bone marrow aspirate, or combinations thereof, toimprove or speed bone regeneration, or resorption and replacement of thebiomaterial. In some examples, the void spaces and/or pores 106 mayfurther accommodate a carrier material that may be incorporated into thevoid spaces and/or pores 106. The carrier material may include, forexample, a collagen sponge, membrane, or a hydrogel material to deliverthe growth factor material such as, for example, the BMP. The calciumphosphate reinforcements 104 exposed on the surface of the porous matrix102, along with the porosity, improves the retention of the BMP withinthe matrix 102 and at the peri-implant interface.

FIG. 5A is an illustration showing a known interbody spinal fusion cage500. The example spinal fusion cage 500 is implanted in theinter-vertebral space 502 between two adjacent vertebrae 506 and 508. Adisc 510, due to degeneration, herniation, etc., is typically removedand replaced by the spinal fusion cage 500. The spinal fusion cage 500is used to support or restore vertebral height, and, thus, stabilize orretain adjacent vertebrae 506 and 508 in a desired position.Additionally, the spinal fusion cage 500 is to promote fusion betweenthe vertebrae 506 and 508.

FIG. 5B is an enlarged illustration of the known spinal fusion cage 500of FIG. 5A. A typical spinal fusion cage 500 includes a body 510 havinga dense outer region 512 and a void 514 at its center. The dense outersurface 512 may be made of PEEK, titanium, or other material that can beused to support the vertebrae 506 and 508. However, the spinal fusioncage 500 made of a PEEK, titanium, etc., cannot attach to the bone.Thus, to promote bone ingrowth, the center void 514 is typicallyprovided with a packing material (not shown) such as, a natural bonegraft, a collagen sponge that retains bone growth factors, or the spinalfusion cage 500 is coated with the bone growth factors or other agentsthat promote osteoinduction.

The example porous scaffold 101 having the composite material 100described herein, and with respect to FIG. 1A, can be implemented withthe spinal fusion cage 500 of FIGS. 5A and 5B to replace the packingmaterials, such as natural bone graft. As noted above, the porousscaffold 101 promotes bone ingrowth and the pores 106 may accommodate ordeliver for example, a BMP, to further improve rate of growth (fusionrate). Furthermore, the calcium phosphate (e.g., HA whisker) binds tothe body 510 and localizes the BMP within the central void 514, whichfurther promotes osteointegration.

FIG. 6 illustrates another example scaffold or matrix 600 implementedwith the example composite material 100 described herein. The examplescaffold 600 may be implemented as an interbody spinal fusion cage. Thescaffold 600 includes a body 602 having a porous polymer matrix 604integrally formed or embedded with anisometric calcium phosphateparticles 606. Furthermore, the matrix 604 of the example scaffold 600includes a radiolucent polymer (e.g., PEEK) integrally formed orembedded with anisometric calcium phosphate reinforcements 606 such as,for example, HA whiskers. The radiolucent polymer provides improvedradiographic analysis of fusion following implantation. The examplescaffold 600 may also include a BMP such as, for example, rhBMP-2. Inanother example, the example scaffold 600 is a biocompatible,microporous polymer scaffold or matrix supplemented with anisometriccalcium phosphate reinforcements and BMP.

Additionally, the example scaffold 600 may formed so that the pores arefunctionally graded in any material or implant direction such as, forexample, radially, as shown in FIG. 6, from a highly porous center orcentral region 608 to relatively dense outer region or surface 610. Thechange in porosity from one region to another may be distinct or gradualfrom the central region 608 to the outer region 610. Further, the gradedchange may be uniform or variant. The dense outer region 610 providesstructural integrity along with the advantages of the composite material100 described herein. In the illustrated example, the porous structure604 has pore sizes that range between about 100 μm and about 500 μm, andpreferably, between about 250 μm and about 500 μm, and a porosity thatranges between about 1% to about 90%. Furthermore, the spinal fusioncage material 600 may include microporosity having pore sizes less thanabout 10 μm.

FIG. 7 illustrates another example scaffold 700. The porous scaffold 700includes a porous matrix 702 having the composite material 100 describedherein. The porous scaffold 700 includes a center or central void 704that may be any shape or size. Additionally or alternatively, thecentral void 704 may receive a material 706, a stem, or any othersubstance or structure, illustratively depicted by dashed lines. Forexample, the central void 704 may receive a stem 706 (e.g., an implant)such as, for example, a titanium stem, a dense composite stem (e.g, aPEEK composite stem), or any other suitable material or structure.

Additionally, in other examples, the scaffold 700 is formed so that thepores are functionally graded in any material or implant direction, forexample, radially as shown in FIG. 7, from a the high porous outerregion or surface 702 to a relatively dense center or central region708. The change in porosity from one region to another may be distinctor gradual from the central region 708 to the highly porous outer region702. Further, the graded change may be uniform or variant. In thismanner, the example scaffold 700 forms a porous perimeter having a densecore, where the material is continuous from the porous perimeter to thedense core. The dense central region 708 provides structural integrityalong with the advantages of the composite material 100 describedherein. In the illustrated example, the porous matrix 702 and the densecentral region 708 may have pore sizes that range between about 100 μmand about 500 μm, and preferably, between about 250 μm and about 500 μm,and a porosity that ranges between about 1% to about 90%. Furthermore,the spinal fusion cage 700 may include a microporosity having pore sizesless than about 10 μm.

In other examples, the composite material 100 and/or the scaffolds 101,600, 700 may also include a roughened surface such as, for example,serrated teeth, that come into direct contact with the adjacentperi-implant tissue to prevent movement relative to the peri-implanttissue after implantation. Additionally or alternatively, although notshown, the scaffolds 101, 600, 700 may include holes, notches, pins,radiographic markers, or other features that may be gripped or otherwiseused for positioning of the scaffolds 101, 600, 700 by minimallyinvasive surgical tools and procedures.

The example composite material 100 and/or the scaffolds 101, 600, 700may be manufactured by methods common to reinforced thermoplastic andthermosetting polymers, including but not limited to injection molding,reaction injection molding, compression molding, transfer molding,extrusion, blow molding, pultrusion, casting/potting, solvent casting,microsphere sintering, fiber weaving, solvent casting, electrospinning,freeze drying (lyophilization), thermally induced phase separation, gasfoaming, and rapid prototyping processes such as solid freeformfabrication, robotic deposition (aka, robocasting), selective lasersintering, fused deposition modeling, three-dimensional printing,laminated object manufacturing, stereolithography, etc., or any othersuitable process(es) or combination(s) thereof.

FIG. 8 is a flowchart of an example method 800 that may be used tosynthesize the example composite material 100 and/or scaffolds 101, 600,700 described herein. While an example manner of synthesizing theexample composite material 100 and/or scaffolds 101, 600, 700 has beenillustrated in FIG. 8, one or more of the steps and/or processesillustrated in FIG. 8 may be combined, divided, re-arranged, omitted,eliminated and/or implemented in any other way. Further still, theexample method of FIG. 8 may include one or more processes and/or stepsin addition to, or instead of, those illustrated in FIG. 8, and/or mayinclude more than one of any or all of the illustrated processes and/orsteps. Further, although the example method is described with referenceto the flow chart illustrated in FIG. 8, persons of ordinary skill inthe art will readily appreciate that many other methods of synthesizingthe example composite material 100 and/or scaffolds 101, 600, 700 mayalternatively be used.

The composite material 100 and/or the scaffolds 101, 600, 700 areprocessed using a powder processing approach in conjunction withcompression molding and particle leaching techniques and is particularlysuited for achieving a high concentration (e.g., >40 vol %) ofwell-dispersed (and aligned, if desired) anisometric calcium phosphatereinforcements (e.g., HA whiskers) in a thermoplastic matrix (e.g.,PEEK) with minimal degradation of the calcium phosphate size/shapeduring processing. In this manner, the calcium phosphate reinforcementvolume fraction, aspect ratio, size and orientation; the polymer; andthe size, volume fraction, shape and directionality of the void spaceand/or porosity may be tailored to vary the mechanical properties of thecomposite material 100 and/or scaffolds 101, 600, 700.

A polymer such as, for example, PEEK, and anisometic calcium phosphateparticles, such as HA whiskers, are provide in powder form (block 802).The PEEK polymer powder may have, for example, a mean particle size ofabout 26 μm. The HA whiskers may be synthesized (block 801) using, forexample, the chelate decomposition method.

The PEEK powder and the synthesized HA whiskers are co-dispersed in afluid (block 804) such as, for example ethanol, and mixed (block 804)using, for example, ultrasonication under constant stirring—forming aviscous suspension.

After the polymer powder and the HA whiskers are mixed, the porosity ofthe mixture is selectively varied and/or tailored (block 806). In oneexample, the porosity may be formed and tailored by the addition of asuitable porogen material such as, for example, NaCl, wax,polysaccharides (sugars), cellulose, etc. The extent of the porosity canbe controlled by varying the amount of porogen used (block 805), whilethe pore size could be tailored by sieving the porogen (block 807) to adesired size prior to mixing the porogen with the polymer mixture. Inanother examples, the porosity and/or the pore size of the polymermatrix may be selectively varied using any other suitable methods and/orprocess(es) such as, for example, microsphere sintering, fiber weaving,solvent casting, electrospinning, freeze drying (lyophilization),thermally induced phase separation, gas foaming, or rapid prototypingprocesses such as, for example, solid freeform fabrication, roboticdeposition (aka, robocasting), selective laser sintering, fuseddeposition modeling, three-dimensional printing, laminated objectmanufacturing, stereolithography, etc., or any other suitableprocess(es) or combination(s) thereof.

The viscous suspension is wet-consolidated (block 808) by, for example,vacuum filtration and drying to remove any residual fluid (i.e.,ethanol). The composite mixture is densified (block 810) by, forexample, uniaxial compression, to form a composite preform.

Following the initial densification, the preform is compression molded(block 812) and/or sintered at elevated temperatures (e.g.,approximately 20° C. to 400° C.) sufficient to fuse the polymerparticles with minimal damage to the calcium phosphate reinforcements.The process or composite material may be heated to a desired processingtemperature and the implant may be shaped or formed (block 814).Densifying and molding the composite material includes aligning thecalcium phosphate reinforcement particles (e.g., HA whiskers)morphologically and/or crystallographically within the scaffold struts.

The scaffold may have any shape and/or size (e.g., any polygonal shape)and can be formed by methods common to reinforced thermoplastic andthermosetting polymers, including but not limited to injection molding,reaction injection molding, compression molding, transfer molding,extrusion, blow molding, pultrusion, casting/potting, solvent casting,and rapid prototyping processes such as, for example, solid freeformfabrication, robotic deposition (aka, robocasting), selective lasersintering, fused deposition modeling, three-dimensional printing,laminated object manufacturing, stereolithography, etc., or any othersuitable process(es). The composite material 100 and/or the scaffolds101, 600, 700, are formed by the mold walls and/or machining aftermolding.

The composite material undergoes a leaching process (block 816) toremove, for example, the porogen used during synthesis of the compositematerial. The leaching may occur, for example, via a dissolution method,heating method, and/or any other suitable methods and/or process(es).More specifically, dissolution may include immersing the scaffold in afluid, such as, for example, deionized water.

Furthermore, viscous flow of the polymer/reinforcement mixture duringmolding can be designed to tailor the preferred orientation of theanisometric reinforcements in the implant. Additionally surface-activeagents may be added during the mixing process and/or to the surface ofthe composite material to enhance interfacial bonding betweenreinforcement particles and the matrix.

The following example is provided to further illustrate the exampleapparatus and methods described herein and, of course, should not beconstrued as in any way limiting in scope. It is to be understood by oneof ordinary skill in the art that the following examples are neithercomprehensive nor exhaustive of the many types of methods and apparatuswhich may be prepared in accordance with the present disclosure.

In the example, commercially available PEKK and sodium chloride (NaCl)powders with mean particle sizes of 70 and 250 μm, respectively, wereused as-received. HA whiskers were synthesized using the chelatedecomposition method. The as-synthesized HA whiskers were measured byoptical microscopy to have a mean length of 21.6 μm, width of 2.8 μm andaspect ratio of 7.6.

In the example, composite scaffolds with 75, 82.5 and 90% porosity wereprocessed with 0-40 vol % HA whisker reinforcement. Appropriate amountsof polymer powder and HA whiskers were co-dispersed in ethanol via asonic dismembrator and mechanical stirring at 1200 rpm. Followingdispersion, the appropriate amount of the NaCl (i.e, porogen) was addedto the suspension and mixed by hand using a Teflon coated spatula. Thetotal scaffold volume consisted of the material volume plus the porevolume. Thus, the reinforcement level was calculated based the desiredmaterial volume, while the porosity level was calculated based on thetotal scaffold volume. After mixing, the viscous suspension waswet-consolidated using vacuum filtration. The powder mixture was driedovernight in a forced convection oven at 90° C. and densified at 125 MPain a cylindrical pellet die using a hydraulic platen press. The die anddensified powder mixture was heated in a vacuum oven to the desiredprocessing temperature and transferred to a hydraulic platen press forcompression molding. Scaffolds with 82.5 and 90% porosity were molded at350° C., while scaffolds with 75% porosity were molded at 350, 365 and375° C. A pressure of 250 MPa was applied to the die as the polymersolidified. After cooling to room temperature, the sintered compositepellet was ejected from the die and placed approximately 300 mLdeionized water for at least 72 h to dissolve the NaCl crystals. Thedeionized water was changed daily. The as-molded composite scaffolds hada diameter of 1 cm and were machined to a height of 1 cm.

In the example, un-confined compression tests were performed toinvestigate the mechanical properties of the composite scaffolds.Specimens were tested on an electromagnetic test instrument in phosphatebuffered saline (PBS) at 37° C. using a crosshead speed of 1 mm/min.Force-displacement data was used to calculate the elastic modulus,compressive yield stress (CYS), and failure strain of the compositescaffolds. One-way analysis of variance (ANOVA) was used to comparemechanical properties between experimental groups. The compressiveproperties of HA whisker reinforced PEKK scaffolds were tabulated intable 1.

The table below provides mechanical properties of the example PEKKscaffold reinforced with HA whiskers that was processed using acompression molding/particle leaching method such as, for example, themethod 800 of FIG. 8 as implemented in the description above. Themechanical properties of HA whisker reinforced PEKK were evaluated inuniaxial compression. Tensile properties of the HA whisker reinforcedPEKK scaffolds were evaluated prior to scaffold fabrication.

Molding Poros- HA Temper- Elastic Yield ity Content ature Modulus CYSStrain (%) (Vol %) (° C.) (MPa) (MPa) (%) 75 0 350 69.5 (12.2) 1.25(0.16) 5.7 (0.4) 75 0 365 100.7 (10.7) 2.04 (0.26) 4.4 (1.2) 75 0 37595.6 (10.5) 2.55 (0.34) 4.4 (1.1) 75 20 350 106.3 (15.0) 1.28 (0.13) 3.7(1.1) 75 20 365 115.4 (13.4) 1.77 (0.30) 2.9 (0.6) 75 20 375 141.1(39.2) 2.28 (0.35) 2.9 (0.7) 75 40 350 54.0 (18.3) 0.52 (0.17) 2.2 (0.3)75 40 365 84.3 (41.5) 1.15 (0.38) 2.7 (0.5) 75 40 375 120.2 (29.8) 1.65(0.34) 2.3 (1.9) 82 40 350 15.7 (6.7) 0.13 (0.03) 2.6 (1.9) 90 0 3500.75 (0.18) 0.15 (0.04) 30 (0.0) 90 40 350 0.23 (0.13) 0.04 (0.01) 30(0.0)

As shown in the table, for a given reinforcement level, the compressivemodulus decreased with increased porosity, and the yield strengthdecreased with increased porosity. Scaffolds with 0% vol % HA whiskerreinforcement and 75% and 90% porosity exhibited moduli of 69.5 and 0.75MPa, while scaffolds with 40 vol % HA whisker reinforcement and 75%, 82%and 90% porosity exhibited moduli of 54.0, 15.7 and 0.23 MPa,respectively. Scaffolds with 0 vol % HA whisker reinforcement and 75%and 90% porosity exhibited yield strengths of 1.25 MPa and 0.15 MPa,respectively. Scaffolds with 40 vol % HA whisker reinforcement and 75%,82% and 90% porosity exhibited yield strengths of 0.52 MPa, 0.13 MPa and0.04 MPa, respectively. The HA content also affected the modulus andfailure strain of the scaffolds. A scaffold having 75% porosity and 20vol % reinforcement HA whisker exhibited modulus of 106.3 MPa, comparedto a modulus of 69.5 MPa for scaffolds with 0 vol % HA whiskerreinforcement.

The example methods and apparatus described herein offer syntheticporous composite material that may be used for synthetic bonesubstitutes for impant fixation, fraction fixation, synthetic bone graftsubstitutes, interbody spinal fusion, tissue engineering scaffolds, orother applications. Many aspects of the of the porous composite materialmay be tailored to provide specific mechanical, biological, and surgicalfunctions, such as, the polymer composition and molecular orientation,porosity and pore size of the porous matrix, or the HA reinforcementcontent, morphology, preferred orientation, and size.

Although the teachings of the present disclosure have been illustratedin connection with certain examples, there is no intent to limit thepresent disclosure to such examples. On the contrary, the intention ofthis application is to cover all modifications and examples fairlyfalling within the scope of the appended claims either literally orunder the doctrine of equivalents.

What we claim is:
 1. A porous reinforced composite scaffold material,comprising: a polyaryletherketone polymer, and a plurality ofanisometric reinforcement particles comprising calcium phosphatecrystals distributed essentially uniformly throughout thepolyaryletherketone polymer; wherein the reinforced composite scaffoldmaterial comprises a substantially continuously interconnected pluralityof pores that are uniformly distributed throughout thepolyaryletherketone polymer, each of the pores in the plurality of poresdefined by voids interconnected by struts, and having a size within therange from about 10 to 500 μm, and wherein anisometric reinforcementparticles are both embedded within the polyaryletherketone polymer andexposed on the struts within the pore voids, and wherein the anisometricreinforcement particles are present from about 1 to about 60%, byvolume, in the polyaryletherketone polymer, and wherein the scaffold isformed by mixing particles of the polymer, reinforcement particles, andparticles of a porogen within a fluid to obtain a substantially uniformmixture, removing the fluid, molding the particle mixture at atemperature from between 20 to 400 degrees C., and removing the porogenparticles.
 2. The porous reinforced composite scaffold materialaccording to claim 1, wherein the porosity ranges between 1 to 95percent by volume.
 3. The porous reinforced composite scaffold materialaccording to claim 1, wherein the anisometric reinforcement particlescomprise one or more of hydroxyapatite, calcium-deficienthydroxyapatite, carbonated calcium hydroxyapatite, beta-tricalciumphosphate (beta-TCP), alpha-tricalcium phosphate (alpha-TCP), amorphouscalcium phosphate (ACP), octacalcium phosphate (OCP), tetracalciumphosphate, biphasic calcium phosphate (BCP), anhydrous dicalciumphosphate (DCPA), dicalcium phosphate dihydrate (DCPD), anhydrousmonocalcium phosphate (MCPA), monocalcium phosphate monohydrate (MCPM),and combinations thereof, and, wherein the polyaryletherketone polymercomprises one or more of polyetheretherketone (PEEK),polyetherketonekteone (PEKK), and polyetherketone (PEK).
 4. A porousreinforced composite scaffold material as described in claim 3, whereinthe anisometric reinforcement particles comprise hydroxyapatitewhiskers, and wherein the scaffold comprises between 1 to 50 percent byvolume of hydroxyapatite whiskers.
 5. The porous reinforced compositescaffold material according to claim 1, wherein the anisometricreinforcement particles have a mean aspect ratio (length alongc-axis/length along a-axis) of greater than 1 and less than
 100. 6. Theporous reinforced composite scaffold material according to claim 5,wherein the size of the anisometric reinforcement particles rangesbetween 20 nm and 2 mm.
 7. The porous reinforced composite scaffoldmaterial according to claim 5, comprising one or more additives selectedfrom growth factors, transcription factors, matrix metalloproteinases,peptides, proteins, bone cells, progenitor cells, blood plasma, bonemarrow aspirate, and combinations thereof, and wherein the one or moreadditives coat the scaffold material, or are contained within some orall of the pore void space, or combinations of these.
 8. The porousreinforced composite scaffold material according to claim 7, comprisinga Bone Morphogenetic Protein (BMP).
 9. The porous reinforced compositescaffold material according to claim 1, wherein the scaffold material ispart of a synthetic bone graft, a bone ingrowth surface applied to anexisting implant, or tissue scaffold.
 10. The porous reinforcedcomposite scaffold material according to claim 5, wherein the porosityis either variable or uniform from a center of the material to anexterior surface.
 11. The porous reinforced composite scaffold materialas described in according to claim 10, wherein the porosity is eitherfunctionally graded radially from a highly porous center to a relativelydense exterior surface or functionally graded radially from a relativelydense center to a highly porous exterior surface.
 12. The porousreinforced composite scaffold material according to claim 1, furthercomprising one or a plurality of any one or combination of featuresselected from holes, notches, pins, radiographic markers, and grippingfeatures.
 13. A porous reinforced composite scaffold material,comprising: a polyaryletherketone polymer and a plurality of anisometricreinforcement particles distributed essentially uniformly throughout thepolyaryletherketone polymer, wherein the reinforced composite scaffoldmaterial comprises a substantially continuously interconnected pluralityof pores that are uniformly distributed throughout thepolyaryletherketone polymer, the pores defined by voids interconnectedby struts; and wherein each of the pores in the plurality of pores has asize within the range from about 10 to 500 μm; and wherein at least aportion of the plurality of anisometric reinforcement particles areembedded in and extend from a strut surface into a pore void; andwherein the anisometric reinforcement particles are present from about 1to about 60%, by volume, in the polyaryletherketone polymer, and whereinthe scaffold is formed by mixing particles of the polymer,reinforcement, and a porogen within a fluid to obtain a substantiallyuniform mixture, removing the fluid, molding the particle mixture at atemperature from between 20 to 400 degrees C., and removing the porogen;and wherein the porous reinforced composite scaffold material has acompressive elastic modulus similar to that of trabecular bone.
 14. Theporous reinforced composite scaffold material according to claim 1,wherein the porogen particles that are mixed with the polymer particlesand the reinforcement particles are either homogenous or heterogeneousin shape and are either homogeneous or heterogeneous in size, theporogen particle size within the range from about 10 to 500 μm.
 15. Theporous reinforced composite scaffold material according to claim 1,wherein each of the pores in the plurality of pores has a void size andshape defined by the removed porogen particles.
 16. The porousreinforced composite scaffold material according to claim 1, wherein theporogen particles are selected from the group consisting of NaCl, wax,polysaccharides, cellulose, and combinations thereof.
 17. The porousreinforced composite scaffold material according to claim 1, wherein theporogen particles have been removed from the porous reinforced compositescaffold material by leaching.
 18. The porous reinforced compositescaffold material according to claim 1, wherein the pore struts comprisea textured surface that is defined by the anisometric reinforcementparticles that are both embedded within the polyaryletherketone polymerand exposed on the struts.
 19. The porous reinforced composite scaffoldmaterial according to claim 18, wherein the textured surface of thepores comprises a plurality of anisometric reinforcement particlesoriented on the surface of the polyaryletherketone polymer.
 20. Theporous reinforced composite scaffold material according to claim 1,wherein the textured surface of the pores comprises a plurality ofanisometric reinforcement particles oriented on the surface of thepolyaryletherketone polymer.
 21. The porous reinforced compositescaffold material according to claim 1, wherein the porogen particleshave been removed from the composite scaffold material by leaching.